This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Exacerbations of chronic obstructive pulmonary disease impose a considerable burden with regard to morbidity, mortality, and health care cost. In the year 2000, COPD exacerbations were responsible for 726,000 hospitalizations, and 119,000 deaths in the US. Based on data from the Agency for Healthcare Research and Quality, patients admitted to US hospitals for COPD in 2002 had a mean length of stay of 5.1 days and accounted for $15,400 in charges. Current management of COPD exacerbations includes bronchodilators, corticosteroids, and antibiotics. Because leukotrienes may play an important role in COPD exacerbations, we propose to study whether anti-leukotriene therapy provides additional benefit to usual care in the management of COPD exacerbations requiring inpatient care. The rationale for anti-leukotriene therapy in acute exacerbations of COPD is based on studies of mediators of inflammation in COPD, on clinical trials of anti-leukotriene therapy in COPD, and on a clinical trial of anti-leukotriene therapy in exacerbations of asthma. The motivation for identification of a novel therapeutic approach to COPD exacerbations is that a reduction in hospital length of stay should result in significant cost savings in the management of this common condition. Clinical studies of the role of leukotrienes in COPD exacerbations indicate that leukotriene levels are elevated in acute exacerbations of COPD, that these elevations are associated with the severity of exacerbation, that levels drop with treatment of the exacerbation and that leukotriene B4 (LTB4)contributes significantly to the neutrophil chemotactic activity of sputum. Shindo et al. demonstrated that mean plasma leukotriene E4 (LTE4) levels in patients with COPD are elevated during acute exacerbation before treatment. They also found that LTE4 levels correlated with PaO2 and FEV1 in patients during acute exacerbation before prednisolone treatment, suggesting that elevated LTE4 levels are a risk factor for more severe exacerbations. The purpose of this study is to test the safety and efficacy of oral zileuton (a 5-lipoxygenase inhibitor) in addition to usual care for treatment of acute exacerbations of COPD requiring inpatient care.